linical trials, which give perilously ill patients a chance to live, often go unfilled in a disconnect that hurts patients and researchers alike.
If you’ve heard about clinical trials for cancer treatments in the past, you’ve probably heard stories like Evan Rose’s. Rose was diagnosed with a rare form of sarcoma in San Francisco in 2007. With few conventional treatment options, Rose, a 49-year-old urban designer, researched clinical trials.
He learned about a trial to investigate a process called TumorGraft. Researchers take pieces of a patient’s tumor, implant them in lab mice, and screen a number of drug regimens on the mice in hopes of finding a combination likely to work on that particular patient.
“I thought, let’s have the mice be the guinea pigs for a change, not me,” Rose said.
Rose persuaded his doctors, who were skeptical at first, to help him participate in the trial. (They had to provide a tumor sample and help devise the list of medications to be tested.) Rose paid for the process out of pocket, at no small expense, eventually moving to New York to be closer to one supportive doctor.
It paid off.
“One of my doctors told me frankly that I wasn’t going to make it through the year” — 2013 — “unless we could find a chemo that would work. And, voila, the early results on one of the combos were very promising,” Rose said.
“One of my doctors told me frankly that I wasn’t going to make it through the year unless we could find a chemo that would work. And, voila, the early results on one of the combos were very promising.”
—Evan Rose
The drug combination shrank Rose’s tumors enough to make surgery on one of his lungs possible. Rose’s sarcoma eventually became resistant to the drugs, which is not unusual for sarcoma patients. He has signed up for a second round of tests to see if another regimen might shrink the drug-resistant tumors.
“Compared to where we were in January 2013, this is a pretty remarkable place to be,” he said.
Healthline interviewed eight people who participated in cancer research trials, and all gave the experience glowing reviews. Patients described feeling like VIPs, getting top-of-the-line healthcare as study participants.
But the vast majority of patients do not participate in clinical trials; less than 5 percent of adults with cancer do. It’s not because there are too few trials to go around. More than 2 in 10 cancer trials sponsored by the National Cancer Institute between 2000 and 2007 failed to meet their patient recruitment goals.
One in 10 trials must shut down due to lack of participation. Almost 40 percent of all cancer trials that don’t run to completion are cancelled because of low patient participation.
To enroll in a trial, patients must clear a series of hurdles. They must learn about the experimental treatment, meet eligibility criteria to receive it, decide that the potential benefits outweigh the costs and risks, and travel to the trial site for a series of appointments. At each of these stages, the field of would-be participants thins.
Many patients never hear about trials because their doctors don’t recommend them. Among the patients Healthline interviewed, most found out about clinical trials through their own research. The only patients who heard about trials through their doctors were referred to trials those doctors were running themselves.
Advocates say patients are better served with more information, whether or not they decide to participate in trials. But doctors aren’t being callous.
“Cancer is a devastating disease. Doctors are doing the best they can and for whatever reason they don’t know about trials,” said Dr. Leonard Lichtenfeld, deputy chief medical officer at the American Cancer Society.
The clinical trials system puts the burden on already over-busy medical practices to stay informed about ongoing trials, screen patients for eligibility, and walk them through daunting consent forms, doctors told Healthline.
The Mount Sinai Hospital oncologist Dr. Ajai Chari juggles clinical practice and research. He explained that educating patients about clinical trials — and going over consent forms that often exceed 30 pages — slows down the practice’s carefully choreographed flow of patients through timeslots and exam rooms.
“Unless you have a vested interest as a clinician, you’re not going to find the time,” he said.
“The reasons [doctors don’t refer patients to trials] are manifold. One is financial; referring a patient out of practice does not help the bottom line. But one is simply based on wanting to continue to care for that patient.”
—Dr. Matthew Galsky, The Mount Sinai Hospital
But skewed financial incentives also help explain why so few doctors refer patients to clinical trials. If doctors provide radiation or chemotherapy, they can bill for it.
“Physicians are generally unlikely to refer their patients to another provider to enroll in clinical trial when they can offer them a standard treatment,” said Dr. Matthew Galsky, a Mount Sinai oncologist who has researched recruiting barriers for clinical trials.
Lichtenfeld agreed that financial incentives are part of the problem.
“People receive third- and fourth-line chemotherapy and may receive chemo within weeks of death when it’s obvious that the drugs aren’t going to work,” Lichtenfeld said, referring to egregious cases he has heard about. “That issue of financial self-interest is always on the table.”
Doctors likely do not consciously consider finances. Economic incentives may simply tip the scales when doctors are already inclined to believe they can provide the best care for their patients.
“The reasons are manifold. One is financial; referring a patient out of practice does not help the bottom line. But one is simply based on wanting to continue to care for that patient,” Galsky said.
The public’s spotty understanding of how medical research works compounds doctors’ challenges.
For example, researchers and patient advocacy groups have said that many patients are reluctant to participate in trials because they fear they will receive a sugar pill.
In fact, placebos are generally only used in early stage trials, and never when a life-saving treatment is already available. Trials typically compare the best available treatment to the same treatment plus the new drug or protocol that’s being studied.
Alice Gordon, a 62-year-old retired New Jersey teacher, was first diagnosed with breast cancer in 2002. She declined at first to participate in a study mentioned by her doctor because she was scared.
“People think that, ‘If I don’t get the trial medicine, I’m going to get a sugar pill.’ That’s not well explained,” she said. Gordon later participated in a different clinical trial.
“I have heard patients say they don’t want to be a guinea pig and possibly die just to try out a new drug,” said Fran Kamin, a graduate student in the social sciences at Florida Atlantic University. She participated in a national clinical trial for advanced breast cancer in 2011.
“I have heard patients say they don’t want to be a guinea pig and possibly die just to try out a new drug.”
—Fran Kamin
“Maybe because I understand how the process works in general, I didn’t find it that daunting,” Kamin added. “I had nothing to lose.”
But even patients who, like Kamin, understand how trials work may not feel comfortable approaching their own health through the dispassionate lens of science.
“It’s one thing to think of it in the abstract and quite another when you have received a potentially life-threatening diagnosis and are thinking about the ways in which you’re going to treat your disease,” said Meghan Gutierrez, chief program, policy, and communications officer at the Lymphoma Research Foundation. The foundation runs a hotline to educate patients about clinical trials.
Method drives researchers, but passions drive patients. The two don’t always mix well.
For instance, some trials feature experimental treatments that have gotten buzz in the media and within the patient community. These trials generate a lot of interest, but would-be participants sometimes refuse to enroll in randomized trials because they can’t be guaranteed to get the new therapy. Other trials test treatments that few have ever heard of, and patients may see no reason to go through the extra effort to sign up. Randomized trials are the final step before the FDA considers a drug for approval.
“If it’s a life-and-death situation, I’d be way more prone to give it a shot, but for those who are like, ‘Well, we could help out for the benefit of science,’ that’s a tougher choice,” said Dale Smith, a 67-year-old retired Philadelphia resident. Smith participated in a double-blind trial to test a drug on patients who would normally just be monitored.
Andrea Denicoff, R.N., the head of operations for the National Clinical Trials Network at the National Cancer Institute, said both too much hype and too little can make it difficult to enroll trial participants. It’s especially tough when the new treatments have been approved for other uses and patients can get access to them “off-label” to treat their disease.
For instance, said Denicoff, for a time women with breast cancer were so convinced that bone marrow transplants would cure them — even suing insurance companies to cover the surgeries — that it was difficult to complete the studies that eventually showed the risky surgeries did not improve survival rates.
Regulatory requirements designed to protect patients can sometimes be overly rigid.
For instance, the first patients to take an experimental drug must have healthy organs to make sure they can flush out drugs that prove unexpectedly toxic. But, Galsky said, the same criteria may be too limiting in later studies to explore additional uses for the same drug.
Researchers may also lock in narrow eligibility criteria in hopes of producing definitive results for publication. Those trial results may help the drugs get approved. However, they may also make oncologists less likely to prescribe the treatments to patients whose medical histories are more complicated and whose prognoses are bleaker, Galsky said.
Sergei German, 54, researched clinical trials online after being diagnosed with lymphoma in early 2013. A New Yorker, German had access to a number of trial locations nearby. But finding a trial for which he qualified took some finesse.
“You have to be sick, but not too sick,” German said.
“Often times by the time patients feel like they should be seeking clinical trials, they are no longer eligible.”
—Dr. Matthew Galsky, The Mount Sinai Hospital
The strictness of criteria for the ongoing Mount Sinai-based trial he eventually joined — testing an immunotherapy for lymphoma — is a case in point.
“You have to have a tumor which is available for biopsy, close to the surface of the skin, and another that’s available for injection, and you have to have at least one more tumor which is a control,” German said.
“Often times by the time patients feel like they should be seeking clinical trials, they are no longer eligible,” Galsky said.
Some patients are excluded from trials based on geography. Most trials take place in major cancer centers, which are most often found in big cities.
Almost half of all cancer patients live more than an hour away from the nearest clinical trial, according to Galsky’s research. How far away patients live also affects their treatment outcomes.
The prospect of commuting to regular, physically taxing medical appointments can play a major role in a patient’s decision-making process. Patients who travel for experimental treatments sometimes, but not always, receive financial help to cover travel and lodging. The prospect of those travel costs may deter others, according to patients Healthline interviewed.
When Zoe Beck, a 74-year-old resident of Shelton, Connecticut, began to educate herself about bladder cancer after receiving the diagnosis, she chose to go to New York’s Memorial Sloan Kettering Cancer Center partly because of its proximity.
“I saw that a center for excellence was just 70 miles away in New York,” she said. Beck never got experimental treatments, but she provided samples for a study testing new ways to track how well chemotherapy drugs are working.
“They always did it on the days when I was already scheduled for something so I wouldn’t have to schlep in from Connecticut to New York,” Beck said.
After all, time is a cancer patient’s most valuable resource. And chemotherapy is grueling enough that even a relatively short trip like Beck’s can be an ordeal.
“If you have a disease like this, you do not want to have to travel. That to me was a major, major part of my decision. You need the least amount of trauma and distress in your treatment,” said Alice Gordon. She has remained in New Jersey for all of her treatments except for two surgeries performed in New York City.
“If you have a disease like this, you do not want to have to travel. You need the least amount of trauma and distress in your treatment.”
—Alice Gordon
Denicoff, of the National Cancer Institute, underscored just how much some patients want to stay close to home. Some women with breast cancer opt to have their affected breast removed in a mastectomy. If there is a radiation center close by, they could have just the tumor removed, in what’s called a lumpectomy, followed by radiation.
“Here we’ve come up with this successful way to have less morbid care but, due to sheer distance, some patients will choose mastectomy anyway because it’s just easier,” Denicoff said.
Elizabeth Naylor, a 25-year-old middle-school teacher living in a suburb of Boston when she was diagnosed in 2009, had everything going for her and still almost didn’t get the experimental treatment that saved her life.
Boston is home to several of the most highly regarded medical centers in the country. Naylor went for chemotherapy for her non-Hodgkin lymphoma at one of the best cancer treatment and research centers in the world, the Dana-Farber Cancer Institute.
Because she was young and otherwise healthy, the team of doctors that oversaw her care expected chemotherapy to work quickly. But her tumors continued to grow through two rounds of chemotherapy. As Naylor braced for the third round, her primary doctor sat her down and let her know just how dire her situation had become.
“He was upfront with me that he wasn’t giving up on me, but it was really bad,” Naylor said. He gave her about a month to live.
But even as Naylor’s doctor prescribed a difficult treatment with little chance of success, he never mentioned clinical trials, Naylor said. He likely knew that clinical trials were an option: Dana-Farber is currently home to more than 400 cancer trials for adults. Naylor’s doctor is currently leading three trials for non-Hodgkin lymphoma patients.
Naylor and her husband are educated and financially stable. And they had personal connections to leverage. It was Naylor’s father-in-law who came up with the idea of a trial after reaching out to every doctor and nurse he had ever met in several dozen phone calls over a 12-hour period.
Naylor’s father-in-law, Reverend Robert Naylor, managed to get the cell phone number of Dr. Wyndham Wilson, a lymphoma researcher at the National Institutes of Health (NIH) in Bethesda, Maryland. The two called him on a Saturday, and, to Naylor’s surprise, he answered. On Monday she had an appointment.
By a strict accounting of the eligibility criteria for the trial she participated in, Naylor was too sick to qualify. However, the doctors had some wiggle room in determining who was too sick and, seeing her age, they enrolled her anyway.
At the NIH, Naylor received stem cells donated by her sister that were used to make T-cells specially trained to recognize lymphoma cells as intruders. The treatment almost certainly saved her life. She is now cancer free, with withering scars where grapefruit-sized tumors had been.
Throughout the trial, the oncologist Naylor had seen at Dana-Farber spent hours on the phone with her husband, painstakingly explaining the procedures described in the NIH paperwork. He was not lazy or ill informed, by Naylor’s account.
Naylor’s care team at Dana-Farber declined numerous requests for comment.
After Naylor’s Lazarus-like recovery, she met a neighbor facing lymphoma and receiving treatment from the same medical team at Dana-Farber. The team had not referred her to a clinical trial either. Naylor encouraged her neighbor to look for a trial at the NIH, and the she later enrolled in one, Naylor said.
There is no clear bad guy in this story. But with blame spread around, a simple solution will also be hard to find. The challenges will only grow in the coming years as both patients and their cancers are divided into more specific categories based on their genetic traits. Each new potential treatment will have to pass muster in a series of clinical trials.
Still, some efforts have successfully brought together patients, advocacy groups, community doctors, government agencies, and leading researchers to expand patients’ access to cutting-edge treatments. Healthline will explore those trends in upcoming investigative articles.
About the Author:
Cameron Scott is a Healthline news staff reporter. Prior to joining Healthline in 2014, Cameron wrote about robotic prosthetics and stem cell research for a tech blog and about the environment for SFGate.com. Cameron has also had work published in SF Weekly, Mother Jones, and California Lawyer.
Before landing in journalism, Cameron earned a doctorate in comparative literature from Cornell University (cold) and a master’s degree in creative writing from the University of Texas (hot).
In the perfectly mild climes of the Bay Area, Cameron enjoys hiking, running, biking, and swimming in fresh water. He has recently discovered that he can put most these together and called it a triathlon. At rest, Cameron enjoys reading, writing creatively, and the company of well-behaved children and poorly behaved canines.
To offer feedback about this story, please email hrl@healthline.com.
